血栓
医学
溶栓药
纳米医学
材料科学
纤溶剂
褐藻糖胶
纤溶
组织纤溶酶原激活剂
溶栓
药理学
多糖
生物医学工程
化学
内科学
纳米技术
心肌梗塞
纳米颗粒
生物化学
作者
Alina Zenych,Charlène Jacqmarcq,Rachida Aid,Louise Fournier,Laura Marcela Forero Ramirez,Fréderic Chaubet,Thomas Bonnard,Denis Vivien,Didier Letourneur,Cédric Chauvierre
出处
期刊:Biomaterials
[Elsevier]
日期:2021-10-01
卷期号:277: 121102-121102
被引量:19
标识
DOI:10.1016/j.biomaterials.2021.121102
摘要
Intravenous administration of fibrinolytic drugs is the standard treatment of acute thrombotic diseases. However, current fibrinolytics exhibit limited clinical efficacy because of their short plasma half-lives and might trigger hemorrhagic transformations. Therefore, it is mandatory to develop innovative nanomedicine-based solutions for more efficient and safer thrombolysis with biocompatible and biodegradable thrombus-targeted nanocarrier. Herein, fucoidan-functionalized hydrogel polysaccharide submicroparticles with high biocompatibility are elaborated by the inverse miniemulsion/crosslinking method. They are loaded with the gold standard fibrinolytic - alteplase - to direct site-specific fibrinolysis due to nanomolar interactions between fucoidan and P-selectin overexpressed on activated platelets and endothelial cells in the thrombus area. The thrombus targeting properties of these particles are validated in a microfluidic assay containing recombinant P-selectin and activated platelets under arterial and venous blood shear rates as well as in vivo. The experiments on the murine model of acute thromboembolic ischemic stroke support this product's therapeutic efficacy, revealing a faster recanalization rate in the middle cerebral artery than with free alteplase, which reduces post-ischemic cerebral infarct lesions and blood-brain barrier permeability. Altogether, this proof-of-concept study demonstrates the potential of a biomaterial-based targeted nanomedicine for the precise treatment of acute thrombotic events, such as ischemic stroke.
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